RNA editing of the human serotonin 5-HT2C receptor disrupts transactivation of the small G-protein RhoA.

Mol Pharmacol 2004 Jan;65(1):252-6

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

The human serotonin 5-HT2C receptor undergoes adenosineto-inosine RNA editing at five positions, generating multiple receptor isoforms with altered G-protein coupling properties. In the current study, we demonstrate that RNA editing regulates the pattern of intracellular signaling. The non-edited human 5-HT2C receptor isoform INI activates phospholipase D via the G13 heterotrimer G-protein. We present evidence that transactivation of the small G-protein RhoA is required for phospholipase D activation. In contrast, neither transactivation of RhoA nor phospholipase D activation was detected in cells expressing the fully edited VGV isoform. The ability to activate phospholipase C is also reduced in VGV-expressing cells, but not to the extent found for the phospholipase D signal. We conclude that RNA editing represents a novel mechanism for regulating 5-HT2C receptor signaling to pathways linked to actin cytoskeletal organization and regulated exocytosis.

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http://molpharm.aspetjournals.org/cgi/doi/10.1124/mol.65.1.2
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January 2004

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